Regulation of Gene Expressionpehs.psd202.org/documents/rgerdes/1515774753.pdf · Concept 18.1:...

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

PowerPoint® Lecture Presentations for

Biology

Eighth Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

Chapter 18

Regulation of Gene Expression

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Overview: Conducting the Genetic Orchestra

• Prokaryotes and eukaryotes alter gene

expression in response to their changing

environment

• In multicellular eukaryotes, gene expression

regulates development and is responsible for

differences in cell types

• RNA molecules play many roles in regulating

gene expression in eukaryotes


Concept 18.1: Bacteria often respond to environmental change by regulating transcription

• Natural selection has favored bacteria that

produce only the products needed by that cell

• A cell can regulate the production of enzymes

by feedback inhibition or by gene regulation

• Gene expression in bacteria is controlled by

the operon model

Fig. 18-2

Regulation of gene expression

trpE gene

trpD gene

trpC gene

trpB gene

trpA gene

(b) Regulation of enzyme production

(a) Regulation of enzyme activity

Enzyme 1

Enzyme 2

Enzyme 3

Tryptophan

Precursor

Feedback

inhibition


Operons: The Basic Concept

• A cluster of functionally related genes can be

under coordinated control by a single on-off

“switch”

• The regulatory “switch” is a segment of DNA

called an operator usually positioned within

the promoter

• An operon is the entire stretch of DNA that

includes the operator, the promoter, and the

genes that they control


• The operon can be switched off by a protein

repressor

• The repressor prevents gene transcription by

binding to the operator and blocking RNA

polymerase

• The repressor is the product of a separate

regulatory gene


• The repressor can be in an active or inactive

form, depending on the presence of other

molecules

• A corepressor is a molecule that cooperates

with a repressor protein to switch an operon off

• For example, E. coli can synthesize the amino

acid tryptophan


• By default the trp operon is on and the genes

for tryptophan synthesis are transcribed

• When tryptophan is present, it binds to the trp

repressor protein, which turns the operon off

• The repressor is active only in the presence of

its corepressor tryptophan; thus the trp operon

is turned off (repressed) if tryptophan levels are

high

Fig. 18-3

Polypeptide subunits that make up enzymes for tryptophan synthesis

(b) Tryptophan present, repressor active, operon off

Tryptophan (corepressor)

(a) Tryptophan absent, repressor inactive, operon on

No RNA made

Active repressor

mRNA

Protein

DNA

DNA

mRNA 5

Protein Inactive repressor

RNA polymerase

Regulatory gene

Promoter Promoter

trp operon

Genes of operon

Operator

Stop codon Start codon

mRNA

trpA

5

3

trpR trpE trpD trpC trpB

A B C D E

Fig. 18-3a

Polypeptide subunits that make up enzymes for tryptophan synthesis

(a) Tryptophan absent, repressor inactive, operon on

DNA

mRNA 5

Protein Inactive repressor

RNA polymerase

Regulatory gene

Promoter Promoter

trp operon

Genes of operon

Operator

Stop codon Start codon

mRNA

trpA

5

3

trpR trpE trpD trpC trpB

A B C D E

Fig. 18-3b-1



No RNA made

Active repressor

mRNA

Protein

DNA

Fig. 18-3b-2



No RNA made

Active repressor

mRNA

Protein

DNA


Repressible and Inducible Operons: Two Types of Negative Gene Regulation

• A repressible operon is one that is usually on;

binding of a repressor to the operator shuts off

transcription

• The trp operon is a repressible operon

• An inducible operon is one that is usually off; a

molecule called an inducer inactivates the

repressor and turns on transcription


• The lac operon is an inducible operon and

contains genes that code for enzymes used in

the hydrolysis and metabolism of lactose

• By itself, the lac repressor is active and

switches the lac operon off

• A molecule called an inducer inactivates the

repressor to turn the lac operon on

Fig. 18-4

(b) Lactose present, repressor inactive, operon on

(a) Lactose absent, repressor active, operon off

mRNA

Protein

DNA

DNA

mRNA 5

Protein Active repressor

RNA polymerase

Regulatory gene

Promoter

Operator

mRNA 5

3

Inactive repressor

Allolactose (inducer)

5

3

No RNA made

RNA polymerase

Permease Transacetylase

lac operon

-Galactosidase

lacY lacZ lacA lacI

lacI lacZ

Fig. 18-4a

(a) Lactose absent, repressor active, operon off

DNA

Protein Active repressor

RNA polymerase

Regulatory

gene

Promoter

Operator

mRNA 5

3

No RNA made

lacI lacZ

Fig. 18-4b

(b) Lactose present, repressor inactive, operon on

mRNA

Protein

DNA

mRNA 5

Inactive repressor

Allolactose (inducer)

5

3

RNA polymerase

Permease Transacetylase

lac operon

-Galactosidase

lacY lacZ lacA lacI


• Inducible enzymes usually function in catabolic

pathways; their synthesis is induced by a

chemical signal

• Repressible enzymes usually function in

anabolic pathways; their synthesis is repressed

by high levels of the end product

• Regulation of the trp and lac operons involves

negative control of genes because operons are

switched off by the active form of the repressor


Positive Gene Regulation

• Some operons are also subject to positive

control through a stimulatory protein, such as

catabolite activator protein (CAP), an activator

of transcription

• When glucose (a preferred food source of E.

coli) is scarce, CAP is activated by binding with

cyclic AMP

• Activated CAP attaches to the promoter of the

lac operon and increases the affinity of RNA

polymerase, thus accelerating transcription


• When glucose levels increase, CAP detaches

from the lac operon, and transcription returns

to a normal rate

• CAP helps regulate other operons that encode

enzymes used in catabolic pathways

Fig. 18-5

(b) Lactose present, glucose present (cAMP level

low): little lac mRNA synthesized

cAMP

DNA

Inactive lac repressor

Allolactose

Inactive CAP

lacI

CAP-binding site

Promoter

Active CAP

Operator

lacZ

RNA polymerase binds and transcribes

Inactive lac repressor

lacZ

Operator Promoter

DNA

CAP-binding site

lacI

RNA polymerase less likely to bind

Inactive CAP

(a) Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized


Concept 18.2: Eukaryotic gene expression can be regulated at any stage

• All organisms must regulate which genes are

expressed at any given time

• In multicellular organisms gene expression is

essential for cell specialization


Differential Gene Expression

• Almost all the cells in an organism are

genetically identical

• Differences between cell types result from

differential gene expression, the expression

of different genes by cells with the same

genome

• Errors in gene expression can lead to diseases

including cancer

• Gene expression is regulated at many stages

Fig. 18-6

DNA

Signal

Gene

NUCLEUS

Chromatin modification

Chromatin

Gene available

for transcription

Exon

Intron

Tail

RNA

Cap

RNA processing

Primary transcript

mRNA in nucleus

Transport to cytoplasm

mRNA in cytoplasm

Translation

CYTOPLASM

Degradation

of mRNA

Protein processing

Polypeptide

Active protein

Cellular function

Transport to cellular

destination

Degradation

of protein

Transcription

Fig. 18-6a

DNA

Signal

Gene

NUCLEUS

Chromatin modification

Chromatin

Gene available

for transcription

Exon

Intron

Tail

RNA

Cap

RNA processing

Primary transcript

mRNA in nucleus

Transport to cytoplasm

CYTOPLASM

Transcription

Fig. 18-6b

mRNA in cytoplasm

Translation

CYTOPLASM

Degradation

of mRNA

Protein processing

Polypeptide

Active protein

Cellular function

Transport to cellular

destination

Degradation

of protein


Regulation of Chromatin Structure

• Genes within highly packed heterochromatin

are usually not expressed

• Chemical modifications to histones and DNA of

chromatin influence both chromatin structure

and gene expression


Histone Modifications

• In histone acetylation, acetyl groups are

attached to positively charged lysines in

histone tails

• This process loosens chromatin structure,

thereby promoting the initiation of transcription

• The addition of methyl groups (methylation)

can condense chromatin; the addition of

phosphate groups (phosphorylation) next to a

methylated amino acid can loosen chromatin

Animation: DNA Packing

1621DNAPacking_A.html

Fig. 18-7

Histone tails

DNA

double helix

(a) Histone tails protrude outward from a nucleosome

Acetylated histones

Amino acids available for chemical modification

(b) Acetylation of histone tails promotes loose chromatin structure that permits transcription

Unacetylated histones


• The histone code hypothesis proposes that

specific combinations of modifications help

determine chromatin configuration and

influence transcription


DNA Methylation

• DNA methylation, the addition of methyl groups

to certain bases in DNA, is associated with

reduced transcription in some species

• DNA methylation can cause long-term

inactivation of genes in cellular differentiation

• In genomic imprinting, methylation regulates

expression of either the maternal or paternal

alleles of certain genes at the start of

development


Epigenetic Inheritance

• Although the chromatin modifications just

discussed do not alter DNA sequence, they

may be passed to future generations of cells

• The inheritance of traits transmitted by

mechanisms not directly involving the

nucleotide sequence is called epigenetic

inheritance


Regulation of Transcription Initiation

• Chromatin-modifying enzymes provide initial

control of gene expression by making a region

of DNA either more or less able to bind the

transcription machinery


Organization of a Typical Eukaryotic Gene

• Associated with most eukaryotic genes are

control elements, segments of noncoding

DNA that help regulate transcription by binding

certain proteins

• Control elements and the proteins they bind

are critical to the precise regulation of gene

expression in different cell types

Fig. 18-8-1

Enhancer

(distal control elements) Proximal

control elements

Poly-A signal sequence

Termination region

Downstream Promoter

Upstream DNA

Exon Exon Exon Intron Intron

Fig. 18-8-2

Enhancer


control elements


Termination region

Downstream Promoter

Upstream DNA

Exon Exon Exon Intron Intron Cleaved 3 end of primary transcript

Primary RNA transcript

Poly-A signal

Transcription

5


Fig. 18-8-3

Enhancer


control elements


Termination region

Downstream Promoter

Upstream DNA


Exon Exon Exon Intron Intron Cleaved 3 end of primary transcript


Poly-A signal

Transcription

5

RNA processing

Intron RNA

Coding segment

mRNA

5 Cap 5 UTR Start

codon Stop

codon 3 UTR Poly-A

tail

3


The Roles of Transcription Factors

• To initiate transcription, eukaryotic RNA

polymerase requires the assistance of proteins

called transcription factors

• General transcription factors are essential for

the transcription of all protein-coding genes

• In eukaryotes, high levels of transcription of

particular genes depend on control elements

interacting with specific transcription factors


• Proximal control elements are located close to

the promoter

• Distal control elements, groups of which are

called enhancers, may be far away from a

gene or even located in an intron

Enhancers and Specific Transcription Factors


• An activator is a protein that binds to an

enhancer and stimulates transcription of a

gene

• Bound activators cause mediator proteins to

interact with proteins at the promoter

Animation: Initiation of Transcription

1809TranscripInitiationA.html

Fig. 18-9-1

Enhancer TATA box

Promoter Activators

DNA Gene

Distal control element

Fig. 18-9-2

Enhancer TATA box

Promoter Activators

DNA Gene


Group of mediator proteins

DNA-bending

protein

General transcription factors

Fig. 18-9-3

Enhancer TATA box

Promoter Activators

DNA Gene


Group of mediator proteins

DNA-bending

protein

General transcription factors

RNA polymerase II

RNA polymerase II

Transcription initiation complex RNA synthesis


• Some transcription factors function as

repressors, inhibiting expression of a particular

gene

• Some activators and repressors act indirectly

by influencing chromatin structure to promote

or silence transcription

Fig. 18-10

Control elements

Enhancer

Available activators

Albumin gene

(b) Lens cell

Crystallin gene expressed

Available activators

LENS CELL NUCLEUS

LIVER CELL NUCLEUS

Crystallin gene

Promoter

(a) Liver cell

Crystallin gene not expressed

Albumin gene expressed

Albumin gene not expressed


Mechanisms of Post-Transcriptional Regulation

• Transcription alone does not account for gene

expression

• Regulatory mechanisms can operate at various

stages after transcription

• Such mechanisms allow a cell to fine-tune

gene expression rapidly in response to

environmental changes


RNA Processing

• In alternative RNA splicing, different mRNA

molecules are produced from the same primary

transcript, depending on which RNA segments

are treated as exons and which as introns

Animation: RNA Processing

1811RNAProcessingA.html

Fig. 18-11

or

RNA splicing

mRNA


Troponin T gene

Exons

DNA


mRNA Degradation

• The life span of mRNA molecules in the

cytoplasm is a key to determining protein

synthesis

• Eukaryotic mRNA is more long lived than

prokaryotic mRNA

• The mRNA life span is determined in part by

sequences in the leader and trailer regions

Animation: mRNA Degradation

1813mRNADegradationA.html


Initiation of Translation

• The initiation of translation of selected

mRNAs can be blocked by regulatory proteins

that bind to sequences or structures of the

mRNA

• Alternatively, translation of all mRNAs

in a cell may be regulated simultaneously

• For example, translation initiation factors are

simultaneously activated in an egg following

fertilization

Animation: Blocking Translation

1813BlockingTranslationA.html


Protein Processing and Degradation

• After translation, various types of protein

processing, including cleavage and the addition

of chemical groups, are subject to control

• Proteasomes are giant protein complexes that

bind protein molecules and degrade them

Animation: Protein Degradation

Animation: Protein Processing

1812ProteinDegradationA.html

1812ProteinProcessingA.html

Fig. 18-12

Proteasome and ubiquitin to be recycled Proteasome

Protein fragments (peptides) Protein entering a

proteasome

Ubiquitinated protein

Protein to be degraded

Ubiquitin

Regulation of Gene Expressionpehs.psd202.org/documents/rgerdes/1515774753.pdf · Concept 18.1:...

Documents

Transcript of Regulation of Gene Expressionpehs.psd202.org/documents/rgerdes/1515774753.pdf · Concept 18.1:...